*Carcinoma, Hepatocellular *Hepatocellular Cancer *Hepatocellular Carcinoma *4 more
Conditions
Interventions
*Biological: PF-08634404
-Solution for infusion
*Biological: Ipilimumab
-Solution for infusion
-Other Names:
#YERVOY
Sponsors
Kawai Norisuke
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: *18 years of age or older at screening. *Locally advanced or metastatic HCC with diagnosis confirmed by histology/cytology or clinically by AASLD criteria (for patients with cirrhosis). Participants without cirrhosis require histological confirmation of diagnosis. *Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies. *At least 1 measurable (as defined by RECIST 1.1 per investigator) and untreated lesion. *Adequate hepatic, liver, and renal function *No prior systemic therapy for HCC. *ECOG performance status 0 or 1 *Child-Pugh Class A
Exclusion criteria
Exclusion criteria: Key Exclusion Criteria: *Moderate or severe ascites. *History of hepatic encephalopathy. *Participants with known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression. *Clinically significant risk of hemorrhage or fistula. *Participants with any history of another malignancy within 3 years. *History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. *Participants with active autoimmune diseases requiring systemic treatment within the past 2 years. *Clinically significant cardiovascular disease within 6 months prior to the first dose. *Major surgery or severe trauma within 4 weeks prior to the first dose or planned major surgery during the study. *History of severe bleeding tendency or coagulation dysfunction. *History of severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding, including bleeding event due to esophageal and/or gastric varices, within 6 months prior to the first dose. *Participants with acute, chronic or symptomatic infections. *Participants with history of immunodeficiency.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| *Number of Participants With Adverse Events [Time Frame: Through end of study and up to approximately 24 months] -Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention. *Phase 1b: Number of participants with Dose limiting toxicities (DLT) [Time Frame: Through 90 days after the last dose of study intervention; Approximately 24 months] -DLTs are a predefined set of adverse events that are at least possibly related to any or all of the study interventions. The number of participants who experienced DLTs during the DLT observation period. *Phase 2: Confirmed Overall Response Rate (ORR) using RECIST 1.1 as assessed by investigator [Time Frame: Approximately 24 months] -ORR is the proportion of participants with a best overall response (BOR) of confirmed CR or confirmed PR per RECIST 1.1 by investigator. *Phase 2: Recommended dose of PF-08634404 in combination with ipilimumab [Time Frame: Approximately 24 months] -The doses of PF-08634404 and ipilimumab selected to be used in combination based on safety, tolerability, pharmacokinetics, and initial anti-tumor efficacy from Phase 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| *Phase 1b: Confirmed Objective Response Rate (ORR) using RECIST 1.1 as assessed by investigator [Time Frame: Approximately 24 months] -ORR is the proportion of participants with a best overall response of confirmed Complete Response (CR) or confirmed Partial Response (PR) per RECIST 1.1 by investigator. *Duration of Response (DOR) per RECIST 1.1 by investigator [Time Frame: Approximately 24 months] -DOR is the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of first documented disease progression per RECIST 1.1 as assessed by investigator, or death due to any cause, whichever occurs first. *Progression Free Survival (PFS) per RECIST 1.1 by investigator [Time Frame: Approximately 24 months] -PFS is defined as the time from the date of first dose to the date of first documented disease progression per RECIST 1.1 as assessed by investigator, or death due to any cause, whichever occurs first. *Overall Survival (OS) [Time Frame: Approximately 24 months] -OS is defined as the time from the date of first dose to the date of death due to any cause. *Number of Participants With Clinical Laboratory Abnormalities [Time Frame: Time from the date of first dose of study intervention through 30-37 days after last dose of study intervention (assessed up to approximately 24 months)] -Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing *Pharmacokinetics (PK): Serum concentrations of PF-08634404 [Time Frame: Up to 24 months] -Predose and/or postdose concentrations of PF-08634404 in combination with ipilimumab. *Incidence of antidrug antibody against PF-08634404 [Time Frame: Up to 24 months] -To evaluate immunogenicity of PF-08634404 in combination with ipilimumab. | — |
Countries
Japan, Puerto Rico, Taiwan, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed